Process Of Statistic Validation Of Corneal Endothelial Cells Analysed Samples

ABSTRACT

Process of statistic validation of corneal endothelial cells analysed samples”, refers to a process complementary to the conventional process known as cornea specular microscopy, by incorporating information obtained by currently available apparatuses, inferring their statistical, and eventually medical, validity, in order to obtain more accurate diagnosis, and better clinical and/or surgical conducts, in so increasing the quality of this procedure to a new level of medical reliability, with the advantages of avoiding that inadequate exams could be considered as valid ones, contribute to diagnosis accuracy, check validity or infirmity of exams already accomplished, guide the eyes bank in the selection and classification of reliability of donated cornea, make use of equipment currently available in the world to improve their own results, identify exams made with not significant sampling, and demonstrate, in a graphic and in numeric form (statistical-analytical rulers).

This patent refers to a process complementary to the conventionalprocess known corneal specular microscopy, which analyzes, according tothe patient age, quantity and morphology of the cells in the cornealinner tissue (endothelium), the anatomical structure responsible formaintaining cornea vitality. The process works by incorporatinginformation obtained by currently available apparatuses, inferring theirstatistical, and eventually medical, validity, in order to obtain moreaccurate diagnosis, and better clinical and/or surgical conducts, in soincreasing the quality of this procedure to a new level of medicalreliability, with the advantages of avoiding that inadequate exams couldbe considered as valid ones, contribute to diagnosis accuracy, checkvalidity or infirmity of exams already accomplished, guide the eyes bankin the selection and classification of reliability of donated cornea,make use of equipment currently available in the world to improve theirown results, identify exams made with not significant sampling,demonstrate, in a graphic and in numeric form, the values of variablesmeasured in the examined eye, when compared to average expected valuesin the patient's age range, demonstrate to the doctor the cases ofcorneas offering risk in clinical or surgical procedures, additionallydemonstrating the relative error regarding the kind of selected andcalculated sample, demonstrate, for a same surgeon, endothelial cellloss inherent to the different techniques and kinds of intraocularsurgeries (surgeon factor), identify the cases of corneal risk assistingin the planning of medical conduct before a disease, improving thequality of the clinical conduct, the quality of adaptation to contactlenses and assisting in the choice of the better technique and surgicalmaterials, supply data and to enable the use of less sophisticated andolder devices with more accuracy in the accomplishment of cornealspecular microscopy exams, revitalizing their utilization and avoidingtheir obsolescence, minimize sampling errors and make easier theunderstanding of the accomplished exams, allow the doctors who receivethe specular microscopy exam in their desks to perform analysis of theobtained sampling validity before valorizing the results of endothelialcells and morphology, allow the doctors to validate or invalidate examsalready accomplished by their patients and allow future comparison withpast exams considered to be valid.

As is known by technicians in the branches of ophthalmology specularmicroscope industry, corneal specular microscopy exam has as goal toanalyze the quantity and the morphology of the cells of the cornealinternal layer, the endothelium, an anatomical structure responsible formaintaining the cornea vitality (transparency and refractive power).

These cells do not multiply during lifetime; there is a gradual celldeath during lifetime. It is necessary a minimum quantity of these cellsto keep cornea biologically useful to our organism, in other words,transparent and with adequate degree. When these cells populationreaches a critical level cornea loses definitively its transparency,being a cornea transplant the only way to restoring vision to thepatient.

Nowadays there are several devices that examine the corneal endotheliumcells, through image obtained in the cornea specular microscopyperformed by the equipment denominated a specular microscope.

This kind of equipment is used in the ophthalmology, but it is alsonecessary in the eye banking routine, trying to measure the vitality ofthe donated cornea, through an appropriated version of specularmicroscope, as this routine exam improves the success index in corneatransplants.

The current process for analysis of corneal endothelial cells has thefollowing limitations and evident difficulties:

1. Lack of sampling calculation: none of the currently available devicesinform how many cells should be evaluated so that the obtained cellsample would be representative of the total population of these cells inthe cornea. Consequence of this limitation: the exam can be consideredvalid for defining a medical conduct without having a statistical orscientific backing, what could lead to medical acts with falsegrounding.

2. The consequence of this lack of sampling calculation is theappearance of a great quantity of exams with sampling error.

3. In the statistical universe of already performed specular microscopyexams coexist, without identification, exams with and without samplingerror;

4. The current technology does not detect, in already performed exams,that ones with correct sampling.

5. The current technology does not detect, in already performed exams,that ones with incorrect sampling.

6. The evaluated data need to be compared with data of an averagepopulation with the same age range, what does not currently occur.Consequence: found data have distinct connotation for different ages sothat in older individuals a given result can be considered as expected,while for a younger individual this same given result will be indicativeof disease, a fact that is not take in account by the currenttechnology.

7. Reference values are not found in the available devices for thedetection of changed, decreased values, not even values indicating riskfor the ocular health or risk for procedures that have as goal thetreatment of ocular diseases.

8. In case of assuming validity for an exam whose results were obtainedwithout the due methodological rigueur, the consequences of medical actscould bring damages to the patient's ocular tissue and vision.

9. In case of evaluating the vitality of a cornea donated for transplantby sampling of endothelial cells examined by corneal specularmicroscopy, there are the same limitations exposed above.

10. The choice of the better receiver for a donated cornea lacksendothelial cell morphometric ground and lacks computer science helpthat could classify in an objective way the data available for suchpurpose.

11. In the way of making more and more simple and automated the processof imaging the cornea endothelium by corneal specular microscopy,technical resources were lost, which would allow a representativesampling analysis.

There are several kinds of Corneal Specular Microscopes available in themarket, which can be classified according to the existence or not ofcontact with the cornea being examined.

Contact Corneal Specular Microscope: In this device, it is necessary thepresence of physical contact between cornea and the objective lens.

Non-contact Corneal Specular Microscope: In this device, no contact isneeded between cornea being analyzed and the optic part of the deviceobjective lens.

According to the data analysis form, corneal specular microscopes areclassified as follows:

1. Non-automated Corneal Specular Microscope: the equipment does notoffer resources for endothelial evaluation, remaining the operatorresponsible for this evaluation, by means of comparison of theendothelium being analyzed with pre-determined grids that supplyendothelial density and cellular morphology standards: pleomorphism andpolymegatism.

2. Semi-automated Corneal Specular Microscope: This device offersresources for endothelial analysis, however it is necessary theinteraction between the operator, the software and the capturedendothelial image in order to supply the estimate value of theendothelial density and cellular morphology: pleomorphism andpolymegatism.

3. Automated Corneal Specular Microscope: This device offers resourcesfor the endothelial analysis, without the needing to interact with thedevice software or with the captured endothelial image in order tosupply the estimate of the endothelial density and cellular morphology:pleomorphism and polymegatism.

Currently, the Corneal Specular Microscopy Exam is performed as follows:

The cells of the corneal endothelium don't multiply and are disposed ina single, thin layer with a thickness of approximately 5 μm. Theendothelium is evaluated from a sample obtained by a corneal specularmicroscope, this sample is taken in form of an image digitalized fromvideo-capture with a mean microscopic increase of 500 times, whichrepresents approximately 1/16 of an area of 1 mm.

Corneal specular microscopy exam evaluates endothelial density, meancellular size, variation coefficient, percentage of cells with less thansix sides, with six sides and with more than six sides, and shapefactor.

These evaluated data can be commented as follows:

1. Cellular Density:

This parameter has the goal of demonstrating, through sample(s) ofendothelial cells captured by the equipment, the quantity of cellsexistent in each mm² of endothelial surface the posterior face ofcornea. It is noteworthy that, when the cell population falls to acritical low level, cornea lacks definitively its transparency, beingcorneal transplantation the only way of restitute its biologicalfunctions.

2. Endothelial Cells Morphology

2.1. Mean Cellular Size or Mean Cellular Area

These measured cells are disposed in a single layer and have a flattenedform; they are studied in their posterior surface by what is called meancellular area or size.

2.2 Pleomorphism

Morphology of normal endothelial cell is mainly hexagonal in shape, alittle part of these cells population can be a different number ofsides, being less than six sides or more than six sides.

This form of variation of the number of sides is called pleomorphism,and is indicative of a lowering of the functional reserve of thesecells, or even of stress or suffering. This aspect of cellularmorphology is evaluated by the percentage of cells with less than sixsides, with six sides, and with more than six sides.

2.3 Polymegatism

The endothelial cell population presents normally a determined standarddeviation of size around an average size. This dispersion is calledpolymegatism and is also an indicative of decrease in the functionalreserve of these cells or even stress or suffering. This aspect of thesecells morphology is evaluated by the variation coefficient.

2.4 Shape Factor

Other way of studying these cells morphology is through the shapefactor, which indicates the regularity of the hexagonal shape in thesecells.

All of these data which evaluate the cornea endothelium are influencedby age, in other words, present a variation during lifetime.

Besides these factors, there are specific cornea diseases that cancompromise the quantity and vitality of these cells, as well as the useof contact lenses or even the intraocular surgery can cause alterationsin this tissue.

It is important to note that the knowledge of the quantity andcharacteristics of these cells helps the doctor in the conduction of thepatient's case, in the choice of the better conduct, decreases risks,and also is used in eyes banks to define the vitality of corneas donatedfor transplants.

The following factors influence the Endothelium of the Cornea:

3.1 Age

All of these above mentioned data, which evaluate the corneaendothelium, are influenced by age, in other words, present variationduring lifetime and become more pronounced with passing of years.

3.2 Ocular Diseases

Besides these factors, there are specific cornea diseases that cancompromise the quantity and vitality of these cells.

3.3 Contact Lenses

The use of contact lenses can cause important alterations in theendothelial cell morphology, so that the specular microscopy exam is aparameter for a biological monitoring of contact lenses users cornea.

b 3.4 Intraocular Surgery

All intraocular surgical procedure infers to the corneal endothelium acertain loss of its cellularity.

3.5 Cornea Donation

The donated cornea loses vitality until the moment of the transplant.

3.6 Cornea Transplant

The cornea transplant determines a very important endothelial cellularloss so that a transplanted person can need a new transplant.

It is noteworthy that the knowledge of the quantity and characteristicsof these cells helps the doctor in the conduction of the patient's case,in the choice of the better conduct, decreases risks, and also is usedin eyes banks to define the vitality of corneas donated for transplants.

Among the devices available in the market, out of production line,however in use worldwide, or currently in production, the followingspecular microscopes can be mentioned:

BIO-OPTICS LSM 12000, LSM 12000 CT, LSM 2200, LSM 2100E, LSM 2100C, LSM2000C, Konan NONCON ROBO SP-6000, NONCON ROBO PACHY SP-9000, CELL CHECK,SEED SP-500, TOPCON SP 1000 and SP-2000P, TOMEY IN-1100, Keeler Konan,ProEB4, Hexgrid, Procem 4, Cell Max contact-type and non-contact type,confocal microscopes NIDEK CONFOSCAN 3 and CORNEA CONFOCAL HRT II.

What all of these listed devices do is to calculate the median and/ormean and standard deviation for cellular density, average cellular size,variation coefficient, percentage of cells with less than six, six andmore than six sides, and shape factor.

Some devices evaluate few of these parameters, other are more completeand evaluate all them, however none of them supplies the comparative ofthe values found in the patient in exam with the average values met inthe normal population. Besides that, they don't supply any indication ofthe quantity of cells to be evaluated so that the examined sample hasstatistical validity and consequently clinical validity.

All the above listed equipment obtains a cell sample that can bestatistically analyzed. This sample can be considered valid or notvalid, taking in account the confidence level and relative error that anaccurate statistical analysis could supply. None of the listed equipmentaccomplishes this analysis to validate or not the samples obtained bythem, because when developed this preoccupation was not considered.

PROCESS OF STATISTIC VALIDATION OF CORNEAL ENDOTHELIAL CELLS ANALYSEDSAMPLES was developed to overcome the limitations, disadvantages andproblems of the current process, because it will be complementary withcurrent technology, not making it obsolete, but on the contrary, willincorporate the information obtained by currently available equipment,inferring them statistical and consequently clinical validity for betterdefining diagnosis and clinical and/or surgical conducts, byincorporating information obtained by currently available apparatuses,inferring their statistical, and eventually medical, validity, in orderto obtain more accurate diagnosis, and better clinical and/or surgicalconducts, in so increasing the quality of this procedure to a new levelof medical reliability, with the following characteristics:

1. The Process is fed with data supplied from the results of examsaccomplished with any of the corneal specular or confocal microscopes inuse.

2. The Process routine makes found results statistically valid andreproducible, what enables a comparative analysis of exams performed indifferent times, besides a better definition of diagnosis andmedical-ophthalmologic conducts, clinical and/or surgical.

3. The Process guides the examiner to obtain elevated reliability degreefor the cells sample in exam. By reliability degree it can be understoodthat among a great number of done diagnosis there is the least possiblenumber of not diagnosed or false-negative cases, in fact patients thatdid not have their done diagnosis, being unnoticed.

4. The Process demonstrates by sampling whether the found relative erroris small or tolerable, and great or not tolerable.

By relative error can be understood that among a great number of normalcases there is the least possible number of diagnosed or false-positivecases when really they are not, in other words, disease is diagnosed fornormal patients.

5. The Process also supplies the possibility that the operator determinein the software, levels of elevated confidence level in order to makeviable, the sizes of endothelial sample to be obtained in the case instudy. For the determined confidence level the Process will calculatethe respective relative error in the exam being performed, this errorguides the doctor in the process of validate or not the result of thespecular microscopy. The confidence level demonstrate the probabilityexpressed in percentage, in which the confidence interval contains avalue mean found for the variable in study. The confidence intervalintroduces two limits, a superior and an inferior, both relative to themean. The inferior limit is defined by the value of the mean minus thepercentage of the relative error and the superior limit is the value ofthe mean plus the percentage of the relative error (Confidenceinterval=Mean±relative error). Thus the exam performed according to theProcess will make easier future comparisons.

6. Besides these achievements, the Process demonstrates in comparativeform, if the values found (mean and respective reliability interval) arein conformity with average values expected for patient's age or if theywill be considered to be low. In these cases, depending on theirmagnitude, the values can be indicative of risk for certainmedical-ophthalmologic conducts. They also are evidenced graphically.

7. An already performed, past exam can be also submitted to the Processanalysis to verify, in the confidence level chosen by the softwareoperator, the relative error of this exam. Thus, it can be sorted thestatistically valid and the statistically not-valid past exams, turningviable comparisons with present exams.

8. The calculation of the sample size to be obtained under orientationof the Process can be accomplished by two ways:

8.1 By the first way, it is taken in account patient data andepidemiologic corneal data to define the total sample, this method isdenominated of Standard Sample.

8.2 By the second way, it is taken in account patient's endothelial datato make a feedback in the Process so that, based in these values, willbe defined the ideal sampling for the eye in analysis, this method isdenominated of Personalized Sample and is the most objective andaccurate way to accomplish the cornea endothelium sampling calculationfor the best use of all devices for corneal specular microscopy devicesavailable in the world market.

9. In addition, the Process shows to the eye banking technician and tothe doctor whether the cornea in routine exam has measures similar tothat average values expected according to donor's age or is consideredinadequate for transplant, besides assisting in the diseases detection.

The Process of the present patent present has the following advantages:

1. It avoids that inadequately performed exams could eventually anderroneously be considered valid.

2. It contributes to the diagnosis accuracy, improving the conduct andminimizing clinical, medical, and surgical errors.

3. It confers validity or invalidates already performed (past) exams.

4. It guides the eye banking routine in classification of donated corneaviability.

5. It better selects corneas available for transplant.

6. It allows the improvement of results in equipment currently in useworldwide by means of the complementary utilization of the Process.

7. It determines the number of cells that should be included in theimages acquired by specular or confocal microscopes to compose astandard or personalized sample.

8. It statistically validates the sample in the exam accomplished inpatient or donated corneas.

9. It offers reproducibility for the results of these exams.

10. It identifies the exams performed with not significant sampling.

11. It shows, in graphic and numeric form, the values of the variablesmeasured in the eye being examined, in comparison with normal peopleaverage values in the patient age range.

12. It shows to the doctor the cases of corneas offering risk inclinical or surgical procedures, be it by the decrease of theendothelial density, be it by the variation in the cellular morphology,be it by the association of both factors.

13. In addition, it shows the relative error or cut off regarding thetype of selected sample.

14. Results obtained for all variables studied by the Process allowcomparison, in a serial way, with further exams led by the Process.

15. From exams already performed by any brand and model of cornealspecular or confocal microscope, at any past time, without any samplingorientation, when analyzed by the Process, existing sampling error canbe obtained:

15.1 In case of data being valid, these can be compared with examsperformed under the Process orientation.

15.2 In case of data being non-valid, these cannot be compared withexams performed under the Process orientation.

15.3 In case of data being non-valid, however with a relative error veryclose to the planned, the doctor decides if this low difference betweenplanned and calculated error could be disregarded, having in mind thefact that this exam was performed in the past.

16. It shows, for a same surgeon, the endothelial cells loss inherent tothe different techniques and kinds of intraocular surgeries (surgeonfactor).

17. It identifies the cases of risks to the cornea, assisting in theplanning of the medical conduct before a disease, improving the qualityof the clinical conduct, of the contact lenses adaptation and assistingin the choice of the better technique and surgical materials.

18. It allows the device users, even in the simplest and olderequipments, to attain solid results in the performance of cornealspecular microscopy exams, revitalizing equipment utilization. For that,it is sufficient to supply the endothelial density and the number ofcell counting in order to make calculations for the Standard Sample and,in case of equipment that also supply the variation coefficient, thePersonalized Sample can be obtained.

19. The Process does not causes obsolescence of equipments currentlyused, on the contrary, improves their results.

20. The Process minimizes sampling errors and makes easier theunderstanding of the performed exams.

21. It allows the doctors who receive the corneal specular microscopyexam in their desks to accomplish analysis of the sampling validity,obtained before taking values of results of endothelial cellularity andmorphology.

22. It allows the doctors to validate or invalidate exams that theirpatients already have accomplished.

For a better understanding of this invention, the following figures areattached:

FIG. 1, which shows the block diagram of the sequence of the Process ofthe present Patent; and

FIG. 2, which shows the statistical-analytical ruler type graph for agraphic visualization of endothelial data results studied and obtainedby the Process. In this case, the presented ruler is an example of theresult of endothelial density.

The Process for statistical validation of cornea samples and analysis ofcornea endothelial cells here presented is realized by dedicatedsoftware specially developed for accomplishment of the Process from thestatistical data obtained in corneal specular microscopy devicescurrently available in the market, taking in account patient age, havingintegration among referred devices and the Process, being the softwareconjugated or not conjugated to the referred devices, and the processaccomplished in the following sequence:

a. Initially, data of the clinic, examiner doctor, requesting doctor,and corneal specular microscope used in image acquisition areconfigured;

b. Patient data are identified: name, date of birth and age;

c. Routine to be accomplished is requested: to guide an exam beingrealized or to validate an already realized, past exam needed to informpast exam date;

d. Data supplied by the specular microscopy exam are entered:endothelial density, average cellular area, number of counted cells,variation coefficient, cells with less than six, with six, and with morethan six sides, and shape factor (they can be one or more than one);

e. The sampling type is selected: Standard for corneal specularmicroscopes that do not calculate the variation coefficient, orPersonalized in case the variation coefficient is known. When thespecular microscope supplies the variation coefficient the user canchoose between the Standard or Personalized sampling type;

f. Statistical power of the sample to be calculated is determined: 90%to 99% confidence level and 10% to 1% for planned relative error;

g. Sample size and calculated relative error or cut off are determined;

h. Graphic and numeric demonstrations of the sample size are shown:

Graphic and numeric demonstration of the quantity of counted cells andof the number of cells that composes the Standard Sample;

Graphic and numeric demonstration of the quantity of counted cells andof the number of cells that composes the Personalized Sample;

Graphic and numeric demonstration of the quantity of counted cells and,of the number of cells that composes the Standard Sample and of thenumber of cells that composes the Personalized Sample (simultaneously);

i. Numeric visualization of the calculated relative error determined forthe number of cells that composes the chosen sample;

j. Graphic Visualization of the values found for the studied variables:endothelial density, average cellular area, number of counted cells,variation coefficient, cells with less than six, six and more than sixsides, and shape factor, presented in statistical-analytical rulers in arectangular format with stripes (areas) positioned side by side in anydirection (from A to D or from D to A), where:

A. Area indicating values above that expected for the age (located inthe side opposite to degradée color);

B. Area indicating values expected for the age;

C. Area indicating values lower than expected for the age, howeverwithin the biological reserve compatible with a normal function;

D. Area indicating values considered critical for the age; the intensityof the color increases as the evaluated data becomes more critical

E. Arrow indicating the mean of the studied variable;

F. Indicates the inferior limit of the reliability interval (RI) for thestudied variable;

G. Indicates the superior limit of the reliability interval (RI) for thestudied variable; and

F-G segment: represents the reliability interval (RI) which iscalculated as follows: RI=mean±relative error calculated for the totalsample, assuming variable length, accompanying in the used scale, thevalue of the calculated reliability intervalis the, F-G segment and canbe positioned below, within, or above the stripes that define the areas.

k. An area is generated for written considerations about endothelialcells morphometry, endothelial analysis and final conclusions andanother clear area is created for optional description of analyzed data(endothelial density, average cellular area, number of counted cells,variation coefficient, cells with less than six, six and more than sixsides, and shape factor);

l. An area is generated for input of diagnosis found in the endothelialand morphometric analysis of the cornea, and another clear area iscreated for the optional description of the conclusion based on resultsevidenced by the Process, where the doctor makes considerations relativeto the clinical-surgical historic; and

m. The reports are printed:

For exams accomplished under the orientation of the Process:

-   -   Graphics: statistical-analytical rulers for each one of the        studied variables (endothelial density, average cellular area,        variation coefficient, percentage of cells with less than six,        six and more than six sides and shape factor), individually        issued for each eye;    -   Sampling: Type of selected sample: standard or personalized with        respective statistical power (confidence level and relative        error), individually issued for each eye;    -   Descriptive (mean for the studied variables and, if available,        standard deviation), where the data for each eye are presented        in comparative form);    -   Final analysis: descriptive report at choice of the doctor        responsible for the Process, or    -   Complete: compounded by all four reports above described; or

To validate already accomplished exams:

-   -   Sample analyzed with respective statistical power, individually        issued for each eye; or    -   Descriptive (mean of the studied variables), where data for each        eye are presented in comparative form.

1. “PROCESS OF STATISTIC VALIDATION OF CORNEAL ENDOTHELIAL CELLSANALYSED SAMPLES”, realized by dedicated software specially developedfor accomplishment of the Process from the statistical data obtained incorneal specular microscopy devices currently available in the market,characterized by, having integration among referred devices and theProcess, being the software conjugated or not conjugated to the referreddevices, the process taking in account patient age and accomplished fromthe data obtained in the referred devices, in the following sequence:Initially, data of the clinic, examiner doctor, requesting doctor, andcorneal specular microscope used in image acquisition are configured; b.Patient data are identified: name, date of birth and age; c. Routine tobe accomplished is requested: to guide an exam being realized or tovalidate an already realized, past exam (needed to inform past examdate); d. Data supplied by the specular microscopy exam are entered:endothelial density, average cellular area, number of counted cells,variation coefficient, cells with less than six, with six, and with morethan six sides, and shape factor (they can be one or more than one); e.The sampling type is selected: Standard for specular microscopes that donot calculate the variation coefficient, or Personalized in case thevariation coefficient is known, when the specular microscope suppliesthe variation coefficient the user can choose between the Standard orPersonalized sampling type; f. Statistical power of the sample to becalculated is determined: 90% to 99% for confidence level and 10% to 1%for relative error; g. Sample size and calculated relative error aredetermined; h. Graphic and numeric demonstrations of the sample size areshown: Graphic and numeric demonstration of the quantity of countedcells and of the number of cells that composes the Standard Sample;Graphic and numeric demonstration of the quantity of counted cells andof the number of cells that composes the Personalized Sample; Graphicand numeric demonstration of the quantity of counted cells and, of thenumber of cells that composes the Standard Sample and of the number ofcells that composes the Personalized Sample (simultaneously); i. Numericvisualization of the calculated relative error determined for the numberof cells that composes the chosen sample; j. Graphic Visualization ofthe values found for the studied variables: endothelial density, averagecellular area, number of counted cells, variation coefficient, cellswith less than six, six and more than six sides, and shape factor,presented in statistical-analytic rulers in a rectangular format withstripes (areas) positioned side by side in any direction (from A to D orfrom D to A), where: A. Area indicating values above that expected forthe age (located in the side opposite to degradée color); B. Areaindicating values expected for the age; C. Area indicating values lowerthan expected for the age, however within the biological reservecompatible with a normal function; D. area indicating values consideredcritical for the age; the intensity of the color increases as theevaluated data becomes more critical E. Arrow indicating the mean of thestudied variable; F. Indicates the inferior limit of the reliabilityinterval (RI) for the studied variable; G. Indicates the superior limitof the reliability interval (RI) for the studied variable; and F-Gsegment: represents the reliability interval (RI) which is calculated asfollows: RI=mean+/−relative error calculated for the total sample,assuming variable length, accompanying in the used scale, the value ofthe calculated reliability interval, F-G segment and can be positionedbelow, within, or above the stripes that define the areas; is the k. Anarea is generated for written considerations about endothelial cellsmorphometry, endothelial analysis and final conclusions and anotherclear area is created for optional description of analyzed data(endothelial density, average cellular area, number of counted cells,variation coefficient, cells with less than six, six and more than sixsides, and shape factor); l. An clear area is generated for input ofdiagnosis found in the endothelial and morphometric analysis of thecornea, and another clear area is created for the optional descriptionof the conclusion based on results evidenced by the Process, where thedoctor makes considerations relative to the clinical-surgical historic;and m. The reports are printed; For exams accomplished under theorientation of the Process: Graphics: statistical-analytical rulers foreach one of the studied variables (endothelial density, average cellulararea, variation coefficient, percentage of cells with less than six, sixand more than six sides and shape factor), individually issued for eacheye; Sampling: Type of selected sample: standard or personalized withrespective statistical power (confidence level and relative error),individually issued for each eye; Descriptive (mean for the studiedvariables and, if available, standard deviation), where the data foreach eye are presented in comparative form); Final analysis: descriptivereport at choice of the doctor responsible for the Process; or Complete:compounded by all four reports above described; or To validate alreadyaccomplished exams: Sample analyzed with respective statistical power,individually issued for each eye; or Descriptive (mean of the studiedvariables), where data for each eye are presented in comparative form.2. “PROCESS OF STATISTIC VALIDATION OF CORNEAL ENDOTHELIAL CELLSANALYSED SAMPLES”, according to the claim 1, characterized by, the useof data supplied by the results of exam accomplished with any of thecorneal specular or corneal confocal microscopes in operation. 3.“PROCESS OF STATISTIC VALIDATION OF CORNEAL ENDOTHELIAL CELLS ANALYSEDSAMPLES”, according to claim 1, characterized by, turning previouslyfound results statistically valid and reproducible for medical help. 4.“PROCESS OF STATISTIC VALIDATION OF CORNEAL ENDOTHELIAL CELLS ANALYSEDSAMPLES”, according to claim 1, characterized by, obtaining elevatedconfidence level for the cell sample under exam, showing whether thefound relative error in samples is small or tolerable, great or nottolerable and to determine levels of elevated reliability degrees tomake possible that the sample endothelial size be obtained in the casein study.
 5. “PROCESS OF STATISTIC VALIDATION OF CORNEAL ENDOTHELIALCELLS ANALYSED SAMPLES”, according to claim 1, characterized by,allowing that an already accomplished, past exam can also be submittedto Process analysis to verify, in the confidence level chosen by thedoctor, its own relative error or cut off value.
 6. “PROCESS OFSTATISTIC VALIDATION OF CORNEAL ENDOTHELIAL CELLS ANALYSED SAMPLES”,according to claim 1, characterized by, calculation of sample size, inStandard or Personalized form, being obtained under orientation of theProcess.
 7. “PROCESS OF STATISTIC VALIDATION OF CORNEAL ENDOTHELIALCELLS ANALYSED SAMPLES”, according to claim 1, characterized by, showingto the eye banking technician and to the doctor whether the cornea inroutine exam has measures similar to that average values expectedaccording to donor's age or is considered inadequate for transplant,besides assisting in the diseases detection.
 8. “PROCESS OF STATISTICVALIDATION OF CORNEAL ENDOTHELIAL CELLS ANALYSED SAMPLES”, according toclaim 1, characterized by, showing, for a same surgeon, the endothelialcells loss inherent to the different techniques and kinds of intraocularsurgeries (surgeon factor).
 9. “PROCESS OF STATISTIC VALIDATION OFCORNEAL ENDOTHELIAL CELLS ANALYSED SAMPLES”, according to claim 1,characterized by, showing, in graphic and numeric form, the values ofthe variables measured in the eye being examined, in comparison withnormal people average values in the patient age range.
 10. “PROCESS OFSTATISTIC VALIDATION OF CORNEAL ENDOTHELIAL CELLS ANALYSED SAMPLES”,according to claim 1, characterized by, identifying the cases of risksto the cornea, assisting in the planning of the medical conduct. 11.“PROCESS OF STATISTIC VALIDATION OF CORNEAL ENDOTHELIAL CELLS ANALYSEDSAMPLES”, according to claim 1, characterized by, supplying data andallowing the device users, even in the simplest and older equipments, toattain solid results in the performance of corneal specular microscopyexams, revitalizing equipment utilization.
 12. “PROCESS OF STATISTICVALIDATION OF CORNEAL ENDOTHELIAL CELLS ANALYSED SAMPLES”, according toclaim 1, characterized by, allowing the doctors who receive the cornealspecular microscopy exam in their desks to accomplish analysis of thesampling validity, obtained before taking values of results ofendothelial cellularity and morphology.
 13. “PROCESS OF STATISTICVALIDATION OF CORNEAL ENDOTHELIAL CELLS ANALYSED SAMPLES”, according toclaim 1, characterized by, allowing the doctors to validate orinvalidate exams that their patients already have accomplished and theresults allowing comparison, in a serial way, with further exams led bythe Process
 14. “PROCESS OF STATISTIC VALIDATION OF CORNEAL ENDOTHELIALCELLS ANALYSED SAMPLES”, according to claim 1, characterized by,statistical-analytical ruler, for graphic visualization of the valuesfound for the studied variables, in a rectangular format with stripes(areas) positioned side by side in any direction (from A to D or from Dto A) and with F-G segment positioned below, within, or above the areasA, B, C and D.